We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular ...

BACKGROUND Normal ionic perfusate containing butanedione monoxime (BDM), a reversible myofilament inhibitor, could be better than either a high potassium (KCl) or a low calcium (CaCl2) perfusate for long-term cardiac preservation. This hypothesis was tested in 70 isolated guinea pig hearts. METHODS AND RESULTS Three groups--time control (8 hours, 37 degrees C), cold control (22 hours, 3.8 deg...

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour regression. Tumour hypoxia can be detected by non-invasive techniques but the interrelationship between these techniques needs to be better defined. [18F]Fluoromisonidazole (18F-MISO) and Cu-labelled diacetyl-bis(N(4)-methylthiosemicarbazone (Cu-ATSM) PET, and...

Background Normal ionic perfusate containing butanedione monoxime (BDM), a reversible myofilament inhibitor, could be better than either a high potassium (KCl) or a low calcium (CaCl2) perfusate for long-term cardiac preservation. This hypothesis was tested in 70 isolated guinea pig hearts. Methods and Results Three groups time control (8 hours, 370C), cold control (22 hours, 3.80C), and cold+B...

Incubation of spontaneously beating ventricular cardiomyocytes from neonatal rats with prostaglandin E(2) (0.1 microM) or forskolin (0.1 microM) simultaneously increased the rate of cellular contraction and atrial natriuretic peptide (ANP) secretion. Both responses were maximal within 10-20 min of application and were accompanied by three- to fourfold increases in cAMP formation. By contrast, a...

Mutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease for which effective therapeutics do not yet exist. Transgenic rodent models based on over-expression of mutant SOD1 have been developed and these have provided opportunity to test new therapeutic strategies and to s...

Confocal microscopy and the H+-sensitive fluorophore carboxyseminaphthorhodafluor-1 (SNARF-1) were used to measure either intracellular pH (pHi) or extracellular pH (pHo) in isolated, arterially perfused rabbit papillary muscles. Single-excitation, dual-emission fluorescent images of the endocardial surface and underlying myocardium to a depth of 300 μm were simultaneously recorded from perfuse...

The basally located actin cytoskeleton has been demonstrated previously to regulate Cl-secretion from intestinal epithelia via its effects on the Na+-K+-2Cl-cotransporter (NKCC1). In nontransporting epithelia, inhibition of myosin light chain kinase (MLCK) prevents cell-shrinkage-induced activation of NKCC1. The aim of this study was to investigate the role of myosin in the regulation of secret...

Callose and cellulose are fundamental components of the cell wall of pollen tubes and are probably synthesized by distinct enzymes, callose synthase and cellulose synthase, respectively. We examined the distribution of callose synthase and cellulose synthase in tobacco (Nicotiana tabacum) pollen tubes in relation to the dynamics of actin filaments, microtubules, and the endomembrane system usin...

The effects of 2,3-butanedione monoxime (BDM) on intracellular Ca transient and cross-bridge function were studied in frog single ®bres from the anterior tibialis muscle of Rana temporaria (sarcomere length, 2.2 lm; temperature, 2±4 °C). The ̄uorescent dye ̄uo-3 was used to monitor the intracellular free calcium concentration ([Ca]i) during isometric contractions. BDM (1±5 mM) reduced the ampli...